Importance of early screening and prophylactic thyroidectomy in asymptomatic nonindex RET germline carriers

Genetic testing For RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C-cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC), Although noninde x RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 thro ugh June 1999) was set up to compare asymptomatic nonindex patients who wer e grouped by age: < 20 years and greater than or equal to 20 years. Inclusi on criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (greater than or equal to 20 y ears) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels pr eoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterpa rts (< 20 years). There was a close correlation between pT1 MTC and an elev ated basal serum calcitonin level (r = 0.67; Spearman's rho), All three pat ients with lymph node metastases from MTC had elevated basal calcitonin lev els. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calci tonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned po sitive. Pathologic conversion of stimulated serum calcitonin obviously mark s the time in carriers of RET germline mutations when surgery should be sch eduled at the latest to be prophylactic.